UPDATE 4-U.S. panel votes to reject J&J, Zeltia cancer drug

By Bill Berkrot

NEW YORK, July 15 (Reuters) - A Johnson & Johnson and Zeltia SA drug for ovarian cancer should not be approved, as risks of heart and liver toxicity outweigh its limited ability to keep the disease in check, an advisory panel to the U.S. Food and Drug Administration said on Wednesday.

By a vote of 14-1, the panel of cancer experts recommended the agency reject the drug, Yondelis. The FDA typically, but not always, abides by recommendations of its advisory panels.

While the rejection is relatively inconsequential for giant healthcare conglomerate J&J, it represents a major setback for Spanish biotechnology company Zeltia.

Zeltia shares closed down 6.5 percent in Spain prior to the final panel vote. J&J shares rose 1.25 percent to close at $58.96 on the New York Stock Exchange.

JP Morgan analyst Michael Weinstein said in a research note he has removed Yondelis revenue projections from his J&J forecasts, but said the earnings impact will be minimal.

'Expectations for Yondelis were low, and this was by no means one of the higher profile programs in J&J's pipeline, but it is a negative nonetheless,' said Weinstein, who had previously expected Yondelis sales of $275 million in 2012.

Yondelis, known chemically as trabectedin, was approved for the treatment of recurrent ovarian cancer in the Philippines last week, raising hopes it would get a favorable reception from the U.S. advisory committee.

But panelists overwhelmingly felt that the modest 6-week benefit in progression-free survival (PFS) shown in a pivotal late-stage clinical trial did not justify approval. The trial tested Yondelis plus Doxil chemotherapy versus Doxil alone.

J&J's Centocor Ortho Biotech unit and Zeltia said they were committed to working with the FDA to address the committee's concerns.

The panel was asked to vote on whether adding trabectedin to Doxil represented a favorable benefit/risk ratio in this patient population.

While the risk bar is considerably higher for drugs for extremely sick advanced cancer patients than those for chronic diseases, a notable increase in severe and life-threatening adverse events in the Yondelis treatment group swung the vote against the drug.

Those included more than twice as many incidents of pulmonary embolism -- a potentially lethal blockage of the arteries to the lungs. Cardiac adverse events were three times higher in the Yondelis treatment group, and liver enzyme increases that can lead to liver damage were much higher.

Panelists also expressed skepticism about the value of progression-free survival -- the time it takes for the cancer to worsen -- as a primary goal for a type of cancer for which other approved therapies exist.

Many seemed willing to revisit the viability of the drug once overall survival data is known. Final overall survival data will not be available for about 18 to 24 months, the companies said. Interim analysis, which may not be indicative of final data, has so far found no significant difference in overall survival.

Company representatives argued that PFS was a clinically meaningful goal and said the drug could be an important treatment option for relapsed ovarian cancer patients who cannot tolerate platinum-based chemotherapies.

The hearing included emotional testimony from a cancer survivor, who credited Yondelis for her recovery. She had suffered from a different type of advanced cancer that failed to respond to treatment with Eli Lilly and Co's Gemzar or Pfizer Inc's Sutent, but said her tumors disappeared after being treated with Yondelis in a clinical trial.

'Trabectedin has given me back my life,' she said in urging the panel to vote in favor of the drug.

The one panelist who heeded that call and who had had ovarian cancer, said: 'It does look like there is a relatively small but significant group who could benefit from this.'

The committee also voted 13-0 to reject a separate application from J&J for wider use of Doxil. Panel members said benefits did not outweigh risks when a combination of Doxil and an older drug, docetaxel, was used as a first-choice treatment for advanced breast cancer patients.

J&J's Centocor Ortho Biotech said in a statement it 'believes the Doxil-docetaxel combination has an important role in the treatment of advanced breast cancer' and the company would work with the FDA to address the panel's concerns.

(Reporting by Bill Berkrot; additional reporting by Lisa Richwine in Washington; editing by Andre Grenon and Carol Bishopric) Keywords: JOHNSONANDJOHNSON/OVARIAN ([e-mail] [phone]; Reuters Messaging: [e-mail]) COPYRIGHT Copyright Thomson Reuters 2009. All rights reserved. The copying, republication or redistribution of Reuters News Content, including by framing or similar means, is expressly prohibited without the prior written consent of Thomson Reuters.